There is compelling evidence for the involvement of the hippocampus in the processing and storage of information by the nervous system. Furthermore, these functions must be accomplished by the basic units of the hippocampus, the neurons, and their various interconnections. Individual pyramidal neurons in the hippocampus are complex units of integration that dynamically change with their environment. Our long-term objective is to understand how a pyramidal neuron integrates and stores the information it receives from the tens of thousands of excitatory and inhibitory synaptic inputs impinging on its dendrites. Understanding how a pyramidal neuron performs these functions will only come from knowledge about the biophsical properties of these neurons and how they respond to synaptic input. This project focuses on the properties and function of voltage-gated ion channels in pyramidal neuron dendrites. During the previous funding period of this grant, we investigated certain properties of Naplus channels, several different types of Ca2plus channels, and two broad categories of Kplus channels present in the apical dendrites of CA1 pyramidal neurons. In this renewal application we propose to continue our investigation of dendritic channels by focusing on the neuromodulation of these channels, on the further investigation of dendritic Kplus channels, and on the role the different channel types play in synaptic integration and in the induction and expression of synaptic plasticity. We will also investigate voltage-gated channels in basal dendrites of CA1 pyramidal neurons and both apical and basal dendrites of CA3 pyramidal neurons, subicular neurons, dentate granule cells, and pyramidal neurons in the entorhinal cortex. The experiments will utilize hippocampal brain slices, dendritic patch-clamp electrophysiology, and high- speed fluorescence imaging of Ca2plus. Neuronal dendrites are altered in specific ways in epilepsy, Alzheimer's disease, schizophrenia, and many other neurological and psychiatric disorders. We expect that the results of our studies will provide important information about the functional significance of these disease-related changes in dendrites.